A COMPREHENSIVE STUDY ON LITERATURE EVIDENCE, CLINICAL STUDIES AND PRACTICES OF HERBAL DRUGS FOR DIABETIC NEUROPATHY AND CARDIOMYOPATHY

  Diabetes mellitus is a worldwide epidemic disease that eventually advances to a chronic stage and affects different vital organs by intensifying the underlying pathological factors, and through the remodeling of the tissues by the generation of reactive oxygen species leading to the development of respective organ failure. Two such complications are painful neuropathy and cardiomyopathy; both of which are common and progressive complications of diabetes. The symptoms of peripheral neuropathy include tingling, burning, lancinating pain, hyperesthesia, and allodynia. The course of the disease progression may vary from intermittent, mild symptoms to severe chronic, and daily pain; which culminates into poor quality of life. Another complication of diabetes mellitus, diabetic cardiomyopathy, is defined as a ventricular dysfunction disorder that occurs in diabetic patients. The development of the disease is characterized by a hidden subclinical period, during which cellular, structural changes and abnormalities lead to diastolic dysfunction, followed by systolic dysfunction, and terminating into heart failure. Left ventricular hypertrophy, metabolic abnormalities, extracellular matrix changes, small vessel disease, cardiac autonomic neuropathy, insulin resistance, oxidative stress, and apoptosis are the most important pathological advancements that lead to diabetic cardiomyopathy. Various pharmaceutical agents from different pharmacological categories have been proposed for the symptomatic treatment of painful diabetic neuropathy; however, it is a herculean task to select a drug due to the wide range of choices and lack of consistent guidelines for treatment. Similarly, treatment of cardiomyopathy is based on the general therapeutic rules of management of heart failure and no specifications have yet been addressed for this condition. Therefore, more studies are required to improve our knowledge of these complex syndromes. From this perspective, this review is designed to delineate a general overview of neuropathy and cardiomyopathy, referring to the conventional therapies in use and possible unconventional, natural, herbal, and safe treatments for both the above-mentioned complications of diabetes

EFFECT OF TERMINALIA CHEBULA (HARAD) FRUIT EXTRACT ON CARDIOTOXICITY IN STREPTOZOTOCIN INDUCED DIABETIC RATS

Objective: The aim of the study was to explore the protective activity of Terminalia chebula fruit extract on cardiotoxicity in streptozotocin (STZ) induced diabetic rats.Methods: The animals were divided into eight groups of five each and were fed with high fat diet (HFD) except sham control, diabetic control and isoproterenol control. Diabetes was induced by administering single intraperitoneal (i. p.) injection of STZ (0.05 g/kg) in all groups except sham and isoproterenol control and was confirmed by testing blood glucose level after 48 h. Rats were pretreated with ethanolic extract of Terminalia chebula (0.25& 0.5 g/kg/d; per oral (p. o.)), pioglitazone (0.01 g/kg/d), carvedilol (0.002 g/kg/d) and normal saline throughout the study period (14 days). Cardiotoxicity was induced by the administrating two subcutaneous (s. c) injection of isoproterenol (ISO) (0.085 g/kg) at an interval of 24 h. Troponin was checked to confirm cardiotoxicity. The evaluation parameters include initial and final blood glucose level, change in body weight, food efficiency ratio (FER), heart weight-body weight ratio, biochemical estimations and histopathological studies.Results: Pretreatment with Terminalia chebula produced significant (p<0.01) decrease in blood glucose level and heart weight-body weight ratio. It significantly decrease the elevated activity of the cardiac marker enzymes, alanine transaminase (ALT), lactate dehydrogenase (LDH), creatinine kinase (CK-MB) (p<0.01), similar to the standard drug carvedilol in isoproterenol injected rats. Pretreatment with Terminalia chebula showed absence of troponin and lesser degree of necrosis, edema, and myofibrillar degeneration.Conclusion: Terminalia chebula has significant cardioprotective action against cardiotoxicity in STZ induced diabetic rats, which is comparable with standard drugs i.e., pioglitazone and carvedilol.Â

A Clinical Insight into Gestational Diabetes

Pregnancy is a diabetogenic state manifested by insulin resistance and hyperglycaemia. The age group at risk of getting gestational diabetes is between 20 and 39 years in 96.8% of cases. Gestational diabetes is the development of symptoms and signs of diabetes mellitus during pregnancy and the glucose level reverting to normal during puerperium. Depending on the type of population and the diagnostic criteria used, gestational diabetes is said to complicate 1–16% of all pregnancies. Many researchers in American, European and Asian surveys have reported 3–6% of prevalence. Compared with white European women, the prevalence rate for GD is increased approximately elevenfold in women from the Indian subcontinent, eightfold in South East Asia, sixfold and threefold in Arab and black Afro-Caribbean women, respectively. Such figures draw a potent clinical interest towards gestational diabetes (GD), and this chapter attempts to highlight some major aspects of GD in respect to both the mother and the foetus or the newborn specially emphasizing on its management as per the World Health Organization (WHO) and International Federation of Gynaecology and Obstetrics (FIGO)

EFFECT OF ETHANOLIC EXTRACT OF GLYCYRIZZA GLABRA AGAINST STEREPTOZOTOCIN AND HIGH FAT DIET INDUCED DIABETES AND HYPERLIPIDEMIA

Objective: To study the effect of ethanolic extract of Glycyrrhiza glabra against streptozotocin and high-fat-diet-induced diabetes and hyperlipidemia.Methods: The present study was conducted on a 14 d model in which Glycyrrhiza glabra extract was given to Streptozotocin (STZ; 50 mg/kg; i. p.) induced diabetic rats fed with high fat diet (HFD), and its protective effect has been studied. The antihyperlipidemic and antihyperglycemic effects have been evaluated on the basis of physical, biochemical as well as histomorphological parameters.Results: The Glycyrrhiza glabra extract pre-treated group showed a significant decrease in biochemical parameters like Total cholesterol (TC), Triglyceride (TG), High-density lipoprotein (HDL), Lactate dehydrogenase(LDH), Alanine transaminase (ALT) compared with D-HFD group (p<0.01). The pre-treated groups also showed significant protection in physical parameters as compared to D-HFD group (p<0.01) which was also confirmed by histopathological studies. All these results were compared and found to be similar with two standard drugs metformin (500 mg/kg) and atorvastatin (10 mg/Kg).Conclusion: This study concluded that alcoholic extract of Glycyrrhiza glabra (500 mg/kg) has significant antidiabetic and antihyperlipidemic potential against streptozotocin and high-fat diet induced diabetic hyperlipidemic rats comparable to the clinically used drugs.Keywords: Atherosclerosis, Diabetic hyperlipidemia, Diabetes mellitus, Hyperlipidemia, Lipid profile, Streptozotoci

A conglomeration of preclinical models related to myocardial infarction

Cardiovascular diseases are the main source of death and morbidity in developed and developing nations. Animal models are required to propel our understanding of the pathogenesis, increase our knowledge, disease progress, and mechanism behind cardiovascular disorder, providing new approaches focused to improve the diagnostic and the treatment of these pathological conditions and additionally to test various therapeutic ways to deal with tissue regeneration and re-establish heart working following damage. A perfect model framework ought to be reasonable, effectively controlled, reproducible, and physiologically illustrative of human disease, show cardinal signs and pathology that resembles after the human ailment and ethically stable. The decision of selection of animal model should be considered precisely since it influences exploratory results and whether results of the research can be sensibly matched with the human. In this way, no specific technique splendidly reproduces the human disease, and relying upon the model, extra cost burden, resources, infrastructure and the necessity for technical hands, should also be kept under consideration. Here we have discussed and compiled various methods of inducing myocardial infarction in animals, basically by surgery, chemicals and through genetic modification, this may benefit the researchers in getting a complied data regarding various methods through which they can induce myocardial infarction in animals

A REVIEW ON PHYTOPHARMACOLOGICAL ACTIVITY OF ALPINIA GALANGA

Alpinia galanga plant which is associated with family Zingiberaceae is mainly scattered in tropical areas and widely known for ethno medicine. Against fungi and bacteria rhizome extract have a maximum inhibitory effect. Alpinia galanga plant is used in medicine and in food preparation. Rhizome extract of Alpinia galanga have high phenolic and flavonoid contents when compared to leaf extract. Because of elevated phenolic and flavonoid content in rhizome extract of Alpinia galanga there is noticeable antimicrobial as well as radical scavenging potential. It is a well-known official drug thought out the country as integrated contribution of nature. It is commonly used for the management of eczema, coryza, bronchitis, otitis interna, gastritis, ulcers, morbilli and cholera, pityriasis versicolor, to clear the mouth, emaciation. The different parts of the plant have various effects like antifungal, antiprotozoal, antiplatelet, antiviral, antidiabetic, immunomodulatory, antibacterial, anti-oxidant effects, hypolipidemic and many others. The essential oil of A. galanga identified 1, 8-cineol as a bioactive agent having antifeeding activity. An aqueous acetone extract of fruit of Alpinia galanga shows inhibitory effect on melanogenesis (formation of melanin). By using different methods, active constituent namely, 1'-acetochavicol acetate in hexane extract of Alpinia galanga rhizome was investigated for their corrosion inhibition properties. The current review add significant information about its, pharmacological activities, medicinal properties and phytochemical investigations as a traditional drug to cure for a number of diseases. Every fraction of the plant has valuable properties that can deliver humanity. The complete plant will be broadly investigated for further future prospective

Bromelain capped gold nanoparticles as the novel drug delivery carriers to aggrandize effect of the antibiotic levofloxacin

To develop bromelain capped gold nanoparticles (BRN capped Au-NPs) as the effective drug delivery carriers of the antibiotic levofloxacin (LvN) and evaluate antibacterial potential of its bioconjugated form compared to pure LvN. BRN capped Au-NPs were synthesized by in vitro method and bioconjugated to LvN using 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide as activator to form Au-BRN-LvN-NPs. These were characterized for mean particle size by dynamic light scattering analysis, zeta potential by Zetasizer nanosystem analysis and transmission electron microscopy (TEM) on carbon coated TEM copper grids by TEM respectively. Drug loading efficiency of LvN was calculated using UV-visible spectroscopy by standard curve of pure LvN. Antibacterial efficacy of Au-BRN-LvN-NPs and pure LvN was determined by evaluating minimum inhibitory concentration (MIC) against Staphylococcus aureus and Eschereschia coli.Two peaks were observed in Au-BRN-LvNNPs spectrum one at 307 nm and other at 526 nm while one peak in BRN capped Au-NPs at 522 nm during UV spectroscopy suggesting red shift. The drug loading efficiency of LvN was found to be 84.8 ± 2.41 %. The diameter of Au-BRN-LvN-NPs and BRN capped Au-NPs were found to be (58.65 ± 2 nm, 38.11 ± 2 nm), zeta potential (-9.01 mV, -13.8 mV) and surface morphology (~13.2 nm, 11.4 nm) respectively. The MICs against S. aureus and E. coli were found to be (0.128 μg/mL, 1.10 μg/mL) for Au-BRN-LvN-NPs and (0.547 μg/mL, 1.96μg/mL) for pure LvN. The results suggested that BRN capped Au-NPs can be used as effective drug delivery carriers of the antibiotic LvN. The Au-BRN-LvN-NPs exhibited enhanced antibacterial activity compared to pure LvN alone

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Lipids: An insight into the neurodegenerative disorders

Summary: Brain development is a sequential anatomical process characterised by specific well-defined stages of growth and maturation. One of the fundamental and necessary events in the normal development of the central nervous system in vertebrates is the formation of a myelin sheath. This process is influenced by dietary lipids. A number of researches have indicated that the administration of a diet, deficient in essential fatty acids during development causes hypomyelination in the brain. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic signalling in neurons. Lipids may also function as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Several experimental studies have suggested a crucial role of n-3 polyunsaturated fatty acids in membrane formation, as well as clinical role of glycerolipids, glycerophospholipids, and sphingolipids in the attenuation of depression- and anxiety-related behaviours. Hence it can be assumed that polyunsaturated fatty acids may also offer new treatment options (for example, targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes). These lipids could be exploited for improved prevention and treatment. A very interesting and emerging approach in this direction is through ‘Lipidomics’ which is a relatively recent research field that has been driven by rapid advances in technologies such as mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, dual polarisation interferometry and computational methods, coupled with the recognition of the role of lipids in many metabolic diseases such as obesity, atherosclerosis, stroke, hypertension and diabetes. Keywords: Glycerolipids, Glycolipids, Polyunsaturated fatty acids, Neurodegenerative disorders, Sphingolipid

Hepatoprotective potential of ethanolic extract of Aquilaria agallocha leaves against paracetamol induced hepatotoxicity in SD rats

Many traditional systems of medicines employ herbal drugs for the hepatoprotection. Aim of the study was designed to evaluate the hepatoprotective potential of ‘ethanolic extract of Aquilaria agallocha (沉 香Chen Xiang) leaves' (AAE) against paracetamol (PCM) induced hepatotoxicity in SD rats. Group I animals were treated with 1% CMC for 8 days. Group II, III, IV and V animals were first treated with ‘1% CMC’ 1 ml/kg/day, AAE 200 mg/kg/day, AAE 400 mg/kg/day and silymarin 100 mg/kg/day respectively for 7 days and then, orally administered with PCM 3 g/kg b. wt. on 8th day in a single dose. 24 h after the last dosing by PCM, the blood was obtained through the retro-orbital plexus under light anesthesia and the animals were sacrificed. Hepatoprotective potential was assessed by various biochemical parameters such as ALT, AST, ALP, LDH, bilirubin, cholesterol, TP and ALB. Group IV rats showed significant (p < 0.01) decrease in ALT, AST, ALP, LDH, cholesterol, bilirubin, liver wt. and relative liver wt. levels while significant (p < 0.01) increase in final b. wt., TP and ALB levels as compared to group II rats. Hepatoprotective potential of AAE 400 mg/kg/day was comparable to that of standard drug silymarin 100 mg/kg/day. Results of the study were well supported by the histopathological observations. This study confirms that AAE possesses hepatoprotective potential comparable to that of standard drug silymarin as it exhibited comparable protective potential against PCM induced hepatotoxicity in SD rats